The zebrafish has proven to be a valuable model organism for studying hematopoiesis, but relatively little is known about zebrafish immune cell development and functional diversity. Elucidating key aspects of zebrafish lymphocyte development and exploring the breadth of effector functions would provide valuable insight into the evolution of adaptive immunity. We performed single-cell RNA sequencing on ∼70,000 cells from the zebrafish marrow and thymus to establish a gene expression map of zebrafish immune cell development. We uncovered rich cellular diversity in the juvenile and adult zebrafish thymus, elucidated B- and T-cell developmental trajectories, and transcriptionally characterized subsets of hematopoietic stem and progenitor cells and early thymic progenitors. Our analysis permitted the identification of two dendritic-like cell populations and provided evidence in support of the existence of a pre-B cell state. Our results provide critical insights into the landscape of zebrafish immunology and offer a foundation for cellular and genetic studies.
Single-cell analyses reveal early thymic progenitors and pre-B cells in zebrafish
Disclosures: L.I. Zon reported personal fees from Fate Therapeutics, CAMP4 Therapeutics, Amagma Therapeutics, Scholar Rock, Branch Biosciences, Celularity, and Cellarity outside the submitted work. No other disclosures were reported.
- Award Id(s): F30HL152628,T32HL007574,R01HL144780
- Award Id(s): HFSP LT000494/2020-L
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Sara A. Rubin, Chloé S. Baron, Cecilia Pessoa Rodrigues, Madeleine Duran, Alexandra F. Corbin, Song P. Yang, Cole Trapnell, Leonard I. Zon; Single-cell analyses reveal early thymic progenitors and pre-B cells in zebrafish. J Exp Med 5 September 2022; 219 (9): e20220038. doi: https://doi.org/10.1084/jem.20220038
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